title: Phase I study of concurrent high-dose three-dimensional conformal radiotherapy with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small-cell lung cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Eligible patients with unresectable Stage III NSCLC, age ≥ 20 years, performance status 0-1, percent of volume of normal lung receiving 20 GY or more (V(20)) ≤ 30% received three to four cycles of cisplatin (80 mg/m(2) Day 1) and vinorelbine (20 mg/m(2) Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively.
  
  
  RESULTS
  Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V(20) >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41-75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3-4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively.
  
  
  CONCLUSIONS
  72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.
authors.affiliation: Division of Internal Medicine and Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. isekine@ncc.go.jp
authors.forename: Ikuo
authors.initials: I
authors.lastname: Sekine
authors.forename: Minako
authors.initials: M
authors.lastname: Sumi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Hidehito
authors.initials: H
authors.lastname: Horinouchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kubota
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D004947:Esophagus / Q000528:radiation effects; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D058958:Organs at Risk / Q000528:radiation effects; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects* / Q000379:methods; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine